Acute Renal Failure Due to Nontraumatic ...

Renal Failure, 21(5),54:5--549 (1 99!3)

CASE REPORT

Ren Fail Downloaded from informahealthcare.com by University of Oxford on 12/07/14 For personal use only.

Acute Renal Failure Due to filmtraumatic Rhabdomyolysis Following Binge Drinking T. Muthukumar,' V. Jhq, A. Sudl, 2 A.. Wanchoo,2

P. Bambery,2 and V. Sakhujal of Nephrology Postgraduate lnshtute of Medical Fdzicatlnn and' Research Chandzgarh, India 2Dqartrnent of I n t m a l Medinne Postgraduate lnshtute of Medical Filticatwn and Rewarch Chandigarh, India 1 Department

ABSTRACT Nontraumatic rhabdomyolysis is an r'mportan,t but under-recognized cause of acute renal failure. In alcolholics, rhcihdonyyolysis most frequently develop following muscle necrcwis during alco,hol-induced coma, but has also been described rarely in ,those without prolonged coma or seizures. We describe a patient who developed mvoglobinuric acute renal failure requiring dialyas following binge drinking in the absence of convulsions or coma. The renal biopsy sh80wedacuk tub,ular necrosis with pigment casts. Key Words:Nontraumatic rhabdomyolysis; Acute renal failure; Alcohol; Myoglobinuria.

TNTRODUC'ITON Rhabdomyolysis is being increasingly recognized as a cause of acute renal failure (APF) (1). Most commonly, it results from trauma to large muscle groups However, it Address correspondence to: Rofessor Vmay Sakhuja, Head, Department of Nephrology, Postgraduate Institute of Medical Education and Research.Chandigarh 160 012, India. Fax: 91 l'i':Z540401: E-mail: [email protected].

545 Copyright 0 1999 by Marcel Dekker, Inc.

www .dekker .corn

Muthukumar et a].

546


has recently been estimated that as many as 25% of cases of myoglobinuric ARF occur in the setting of nontraumatic rhabdomyolysis (2). The majority of these ARF patients with drug or alcohol induced coma in whom muscle compression on a hard surface results in a high pressure in the intramuscular compartment, causing ischemic muscle necrosis or those with status epilepticus where prolonged muscle contraction leads to necrosis. Alcohol can also cause nontraumatic rhabdomyolysis by other mechanisms (3,4).However, very few cases of ARF due to alcohol induced rhabdomyolysis in the absence of coma or seizures have been reported in the literature (5-7). Here we report a chronic alcoholic who developed rhabdomyolysis leading to acute renal failure following binge drinking.

CASE REPORT A 38-year-old truck driver was admitted to our hospital for treatment of ARF.The patient, a chronic alcohol consumer, was well till four days prior to entry when he developed generalized body ache and weakness involving all four limbs.At the same time, he also noticed a change in the color of urine to dark brown and reduction in quantity of urine to around 250 mL/day. For two days prior to the onset of these symptoms, he had been drinking continuously without taking any food. According to his own estimate, he had consumed about 3000 mL of whisky during this time. There was no history of any alteration in sensorium, convulsions, vomiting, fever, trauma or intake on nonsteroidal anti-inflammatory drugs. Two days after the onset of symptoms, he was taken in a local hospital where he received intravenous fluids, furosemide and vitamin injections. With this treatment, the urine color became normal, but the volume did not improve. At this stage, he was referred to our institute. At entry, the patient was conscious and alert. There was mdd pedal edema but no pallor or purpuric spots. His pulse was 108 beatdmin and the blood pressure was 140/90 mm Hg. Examination of heart, lungs and abdomen revealed no abnormality. Neurological examination revealed mild weakness of proximal muscles of both upper and lower limbs. There was no neck muscle weakness, and all tendon reflexes were normal. The ocular fundi were normal. On investigation, the hemoglobin was 12 gm/dL, total leukocyte count was 12,500/mm3with 80% neutrophils and 16% lymphocytes. The platelet count was 191,000/mm3Urinalysis revealed 2+ protein and 10-12 red blood cells per high power field. The blood urea was 186 mg/dL, creatinine 10 mg/dL, calcium 7.5 mg/dJ+ inorganic phosphate 186 mg/dL, albumin 3.7 gm/dL, AST 128 IUL and ACT 102 I/L respectively. Serum creatinine phosphohnase was 11,240 U/L (normal 24-130 UL). Urine hemoglobin was 2 m@dL, and plasma hemoglobin was 3 mg/dL. Urine for myoglobin done on day three and four after admission was negative. An ultrasound examination revealed the kidneys to be normal sized and there was no hydronephrosis. His chest radiogram and electrocardogramwere normal. A peritoneal dialysis was started soon after admission and later he received regular hemodialysis. A kidney biopsy was done after two weeks of oliguria. Light microscopy revealed one glomerulus that was normal. The tubules showed dilatation and desquamation of lining epithelium. A large number were filled with pigment casts. Focal regenerative activity was also noted. The interstitium showed a smattering of mononuclear cells. Hemodialysis was continued. The urine output started to improve after 20 days of oliguria and was accompanied by a gradual fall in serum creatinine. The serum creatinine fell to 4.3 mg/& after one week of onset of the diuretic phase and he was discharged from the hospital. He has now been followed up for two months. He is asymptomatic and the creatinine has come down to 1.6 m@dL.

ARI; Due to Nontraumatic Rhabdomyolysis

547


DISCUSSION Muscle accounts for approximately two fifthis of total body mass. Any insult to big muscle groups results in muscle fiber Qssolution. and relcase of potentialty toxic iintracellular components into the systemic circulatiion. Renal1 dysfunction complicates' approximately 30% of cases of rhabdomyolysis (1 ), while this condttion accounts for 3 to loo/oof all ARF in various series (5,6). Nontraumatic rhabdomyolysis can occur secondary to ;a number of causes. Thes'e include malignant hyperpyrexia, extreme exertion, repeated seizures, ischemic, metabolic and. inherited disorders of muscles, bacterial anid viral in:ti:ctioins. snake bi.te, idtopathc poiymyositis and drugs (4,5,7-9). In the tropicail countries, nori-traumatic irhabdomyolysis is also observed in conditions such as eclampsia, prolmged labor, mermic chloride or i:inC phosphide poisoning and status asthmaticxs (9.101). Dngs and toxins can cause rhalsdomyolysis by causing coma leadmg to compression of limbs. excessive muscular activity. hyperthermia, vasoconstriction with resultant miuscle ischemia, iimpaired ATP formation, cellular potassium and phosphate depletion, myositis secondary to hypersensitivity reaction and Qrect toxic effects (4.1 1). Ohr patient presented with severe oliguric renail failure ain'd required dialytic support for over two weeks. In a series of 59 patients with non-traumatic rhabdomyolysis. 13.S% developed acute renal failure (8). In another series 'of 30 patients with acute drug associated rhatxiomyolysis, 66% developed ARF,half of tlhem non-c~lliguric(12). Gaktow et al. (7) noted acute renal failure in 33% whle 7% had prerenal azoltiemia(8). Ethyl alcohol is an important cause of non-traiumnatic rhahdomiyolysis. In ;a series of 40 patients with ARF due to nontraumatic rhabdomyolysis, 1'4 were ethanol-induced ( 5 ) . In another series, alcoholism was associated in 67% of 87 episodes of rhabdomyolysis recorded in 77 patients (7). In a series of 903 ARF patients, rhabdomyolysis accounted for 3.1%of all cases of severe renal failure. the commonest caiitse being muscle compression due to drug or alcohol induced coma (6). Ethanol can produce muscle injury in a variety of ways. 'These include trauma.seizures or ischemic muscle necrosis in a comatose individual. Siiice none of these condt1,ions weDe present in our patient, the rhabdomyolysis probably resulted from a chrect toxi'c effect of ethanol on muscles. ARF following ethanol-induced rhabdomyolysis in the absence of coma oir seizures has been reported rarely. Haapanen et al. ( 5 ) reponted seven patients with alcohol-induced rhatxiomyolysis who were neither comatose nor had convulisions at any stage of the Qsease (2). Binge drinlung in association with intake of rionsteroidal anti-inflammatory drugs (NSAIDS) has been reported to lead to ARF in a few case reports (13,14). NSPiIDs ARF thought to predispose to ARF by altering the balance of intrarenal prostaglandin synthesis in favor of the vasoconstrictor thromboxanes. M[uscle Qsease due to alcohol has been classified into am1 acute muscular syndrome, a chralnic progressive muscular weakness and wasting associated with peripheral neuropathy ,and a subclinical Qsease manifesting solely with elevated serum muscle enzymes. The acute muscular syndrome is associated with episodes of' exceptionally heavy alcohol intake and can be associated with overt rhabdomyculysis (15). Alcohol induces substantial changes in muscle ion homeostasis includtng increments in Na'. (31- and Ca" and tfecrements in Mg*, K t and phosphate content. These ARF ass'ociatedwith a heightened Na' -K' .ATPase activity, leaQng to increased Na' entry, with secondary increase in Ca" via enhanced Na'~-Ca* exchange. These changes either initiate or along with the other changes discussed above, predispose to myonecrosis (4).

Muthukumar et al.


548

The mechanism of ARF following rhabdomyolysis is not well understood. A number of intracellular substances, including myoglobin, aldolase, creatine kinase and aspartate aminotransferase ARF released from the injured muscles into the circulation (5). Myoglobin is a protein of molecular weight of daltons and is freely filtered at the glomerulus. It can induce renal damage by producing renal vasoconstriction, intraluminal cast formation and by direct cytotoxicity. Myoglobin has been demonsbrrted at the brush border and in the granular cylinders of the tubular epithelial cells (16). In addition, rhabdomyolysis also causes extensive fluid third spacing, activation of endotoxin-cytokine cascade and nitric oxide scavengingby heme proteins. The resulting vasoconstriction further depletes the renal tubular ATP stores, increasing cast formation and promoting proximal tubular cell heme uptake and increase in production of toxic free oxygen radicals (4). In our patient, the urine tested negative for myoglobin seven days after the onset of symptoms. Absence of myoglobin in the urine does not argue against the diagnosis of rhabdomyolysis. This is likely to be due to the grossly reduced glomerular filtration rate in this patient. In Gabow’s series (7),myoglobin could not be demonstrated in the urine samples of about SO% of patients. A five or more fold increase in serum creatine kinase levels in the absence of cardiac or brain injury can be taken as an evidence of rhabdomyolysis (7).In conclusion, we report a case of a chronic alcohol consumer, who indulged in an episode of exceptionally heavy drinking, developed rhabdomyolysis leading to acute renal failure and needed dialytic support.In the absence of coma or seizures,he probably developed muscle injury because of a direct toxic action of alcohol on muscles. REFERENCES 1

2. 3. 4. 5.

6.

7. 8. 9. 10. 11. 12. 13. 14.

Brady HR, Brmer BM, Liebertha1 W Acute renal failure. In: B r m e r BM ( 4 ) ; The Kidney, 5th ed. WB Saunders, Philadelphia, 1996, pp 1200-1252. Doherty CC: Epidemiology of acute renal failure. In: Davison AM, Cameron JS, M e l d F, et al. (eds); Owford Text Book of ClinicalNephrology, 2nd ed Oxford University press, Oxford, 1998, pp 1521-1530. Song SK, Rubin E: Ethanol produces muscle damage in human volunteers. Science 175:327-328,1972. Zager R A Rhabdomyolysis and myoglobmuricacute renal failure. Kidney Inr 49:3 14-326,1996. Haapancn E, Partanen J, Pellinen T J Acute renal failure following nontraumatic rhabdomyolysis. Scand J Urol Nephrol22:305-308,1988. Woodrow G, Brownjohn AM, Tumey JH: The clinical and biochemical features of acute renal failure due to rhabdomyolysis.Renal Failure 17:467-474, 1995. Gabow PA, Koehny WD, Kelleher SP: The spedrum of rhabdomyolysis. Medicine (Baltimore) 61:141-152,1982. Femandez-Funez A, deTomas E, Alamillo A, et al.: Nontraumatic rhabdomyolysis: its etiology and the predictive factors of acute kidney failure. Med Clin 105:412-415,1995. Chugh KS, Sitpriia V. Jha V: Acute renal failure m a special setting. Tropical countries. In: Davison AM, Cameron JS,Gnmfeid JP, et al.(eds); Oqord f a ? book of Clinical Nephroloo, 2nd ed. Oxford University press, Oxford, 1998, pp 1714-1733. Chugh KS, Singhal PC,Nath IVS, et al.: Acute renal failure due to nontraumatic rhabdomyolysis. PosrgradMed J 55:386-392,1979. Don BR, Rodriguez RA, Humphrey MH: Acute renal failure associated with pigmenturia or aystal de posits. In: SctVier RW, Gottschalk CW (eds); Diseases of the Kidney, 6th ed. Latle,Brown and company, Boston, 1997,pp 1273-1279. Cadwapaphomchai P, Taber S, McDonald F: Acute drug-associated rhabdomyolysis. Am J Med Sci 28066-72, 1980. Tsuboi N, Yoshida H,Shibamura K, et al.: Acute renal failure afler binge drinking of alcohol and nonsteroidal anti-inflammatorydrug ingestion.InfernMed 36:102-106,1997. ENiquez R, Sirvent AE,Antolin A, Cabemelo JB,Gonvllez C, Reyes A: Acute renal failure and Hank pam afler binge drinking and non-steroidal anti-inflammatory drugs. Nephrol Dial Tmnsplunt 12:2034-2035,1997.

ARF Due to Nontraumatic Rhabdomyolysis

549

IS. Saltissi D, Parfrey PS. Curtis JR et al.: Rhabdomyolysiis and acute irtnal fadure in chronic alcoholics wnh


myopathy, unrelated to acute alcohol ingestion. CfrnN q h r o f 21:294-300, 1984. 16. Hsu SM, Weme 4 Chiffhs G , Raine L: Demonstration of myo&bin in formalin-fixed renal semdions renal sections by immunoperoxidasete&nic. A m J Clrn I’ofhol77:3 16-3 19, 1982.